Neocarzinostatin (NCS), which causes DNA strand scission both in vitro and in vivo, reversibly inhibits the growth of both unpermeabilized and lysolecithin-permeabilized P815 mast cells (mouse leukemic cells). Kinetic experiments with NCS-pretreated cells revealed that the permeabilized cells are more strongly affected than the unpermeabilized cells, indicating that the membrane protects the cells against the influence of NCS. The two major DNA polymerase activities (form alpha and form beta) were determined in permeabilized cells during the lag phase of growth, after NCS treatment, and an 8.5-fold higher DNA polymerase beta activity was observed in NCS-treated cells than in controls. The activity of the second enzyme, DNA polymerase alpha, was low during the period of cell proliferation.